In WO 95/27730, Perez Baz et al. disclosed the isolation and the two-dimensional structural elucidation of a new antitumoral agent, Thiocoraline A, from the marine organism Micromonospora sp.

In 1999, Erba et al. reported the activity of this compound as inhibitor of DNA alpha-polimerase at concentrations that inhibit cell cycle progression and clonogenicity (Erba, E.; Bergamaschi, D.; Ronzoni, S.; Faretta, M.; Taverna, S.; Bonfanti, M.; Catapano, C. V.; Faircloth, G.; Jimeno, J.; D'Incalci, M. British J. Cancer 1999, 80, 971-980).
In WO 02/49577, Boger and Lewis disclosed the total synthesis of Thiocoraline A and BE-22179. This total synthesis allowed the elucidation of relative and absolute stereochemistries of Thiocoraline A. They also reported the preparation of Thiocoraline A analogs wherein the 2-hydroxyquinolyl group was replaced with other quinolines or quinoxalines.

They also reported the binding of thiocoraline A, BE-2179 and its analogs to DNA by high-affinity bisintercalation with little or no perceptible sequence selectivity.
Recently, Gago et al. disclosed the X-ray structure of Thiocoraline A and its DNA binding properties (Negri, A.; Marco, E.; Garcia-Hernandez, V.; Domingo, A.; Llamas-Saiz, A. L.; Porto-Sandá, S.; Riguera, R.; Laine, W.; David-Cordonnier, M-H.; Bailly, C.; Garcia-Fernández, L. F.; Vaquero, J. J.; and Gago, F. J. Med. Chem. 2007, 50, 3322-3333).
Thiocoraline A shares several common motifs with a family of antitumoral peptide antibiotics, which includes Triostin A (Shoji, J., et al. J. Antibiot. 1961, 14, 335-339), BE-22179 (Okada, H., et al, J. Antibiot. 1994, 47, 129-135), and Echinomycin (Corbaz, R., et al. Helv. Chim. Acta 1957, 40, 199-204).

This group of 2-fold symmetric or pseudosymmetric bicyclic octapeptides shows a complex structure containing: a) a bicyclic structure formed by two peptide chains in an antiparallel mode; b) an ester or thioester linkage at the terminal part of the peptide chain; c) a disulfide or an analogue bridge in the middle of the peptide chains; d) an intercalation chromophore moiety at the N-terminal part; e) the presence of several N-methyl amino acids; and f) non natural amino acid of D configuration.
Boger and Lee reported in 2000 the synthesis and cytotoxic activity against leukemia cell line L1210 of Azatriostin A (Boger, D. L.; Lee, J. K. J. Org. Chem. 2000, 65(19), 5996-6000). Azatriostin A is a Triostin A analogue wherein the ester linkage at the terminal part of the peptide chain has been replaced with an amide linkage. Azatriostin A was two orders of magnitude less active than Triostin A against this cell line.
Other Thiocoraline A analogs disclosed in the prior art are Oxathiocoraline, which shown cytotoxic activity against three cell lines with GI50 values between 3.0E-7 M to 4.62E-7 M (Tulla-Puche, J.; Bayó-Puxan, N.; Moreno, J. A.; Francesch, A. M.; Cuevas, C.; Álvarez, M.; and Albericio, F. J. Am. Chem. Soc. 2007, 129, 5322-5323), and Azathiocoraline, which shown cytotoxic activity against a panel of cell lines with GI50 values between 5.67E-6 M to 2.58E-7 M (Bayó-Puxan, N.; Fernández, A.; Tulla-Puche J.; Riego, E.; Cuevas, C.; Álvarez, M.; and Albericio, F. Chem. Eur. J. 2006, 12, 9001-9009; Bayó-Puxan, N. Ph. D. Thesis, University of Barcelona, 2006), and Azathiocoraline analogs wherein the intercalation chromophore moeity at the N-terminal part of Thiocoraline A and/or a cyclic amino acid was modified (Bayó-Puxan, N.; Fernández, A.; Tulla-Puche J.; Riego, E.;. Álvarez, M.; and Albericio, F. Int. J. of Peptide Research and Therapeutics. 2007, 13, 295-306).
 CompoundXZR1R2R3OxathiocoralineOCH—CH2—SMeOHOHAzathiocoralineNHCH—CH2—SMeOHOH[NMe-Leu4, NMe-Leu8]azathiocoralineNHCHi-PrOHOH Azathiocoraline + 3HQANHCH—CH2—SMeOH [2QXA, NMe-Ala4] AzathiocoralineNHNMeHH[2QNA, NMe-Ala4] AzathiocoralineNHCHMeHH
Compounds [NMe-Leu4, NMe-Leu8] Azathiocoraline, [2QXA, NMe-Ala4] Azathiocoraline, and [2QXA, NMe-Ala4] Azathiocoraline were also tested against this cell panel with GI50 values higher than 9.99 E-6 M (Bayó-Puxan, N. Ph. D. Thesis, University of Barcelona, 2006).
Cancer is a leading cause of death in animals and humans. Huge efforts have been and are still being undertaken in order to obtain an antitumor agents that are active and safe to be administered to patients suffering from a cancer. The problem to be solved by the present invention is to provide compounds that are useful in the treatment of cancer.